French national cohort of first use of dalbavancin: a high proportion of off-label use

Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft tissue infections (SSTI), but real-life use is not well-known. We aimed to describe all first prescriptions in France over an 18-month period. We performed a retrospective study on all adult patients who received at least one dose of dalbavancin from July 1, 2017 to September 31, 2018. Data were collected thanks to a standard questionnaire. Failure was defined as: persistent or reappearance of signs of infection; and/or switch to suppressive antibiotic treatment; and/or death from infection. We included 75 patients from 29 French hospitals. Main indications were bone and joint infections (BJIs) (64.0%), endocarditis (25.3%), and SSTIs (17.3%). Main bacteria involved were: Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%); and coagulase-negative staphylococci (CNS) (44.4%). Median MICs for staphylococci to vancomycin and dalbavancin ranged from 0.875 mg/L to 2.0 mg/L, and 0.040 mg/L to 0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. Main treatment regimens for dalbavancin were a weekly 2-dose regimen (1500mg each) in 38 (53.2%) cases, and a single-dose regimen (1500mg) in 13 (18.3%) cases. Overall, at the patients\u27 last visit, clinical cure was observed in 54/72 patients, while failure was found in 14/72 patients. First uses of dalbavancin in France were mostly off-label. Most of them were due to BJIs, and often as rescue therapy for severe infections. Even in off-label situations, dalbavancin seems safe and effective

Endangered edible orchids and vulnerable gatherers in the context of HIV/AIDS in the Southern Highlands of Tanzania

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Design and development of a field-deployable single-molecule detector (SMD) for the analysis of molecular markers

Single-molecule detection (SMD) has demonstrated some attractive benefits for many types of biomolecular analyses including enhanced processing speed by eliminating processing steps, elimination of ensemble averaging and single-molecule sensitivity. However, it's wide spread use has been hampered by the complex instrumentation required for its implementation when using fluorescence as the readout modality. We report herein a simple and compact fluorescence single-molecule instrument that is straightforward to operate and consisted of fiber optics directly coupled to a microfluidic device. The integrated fiber optics served as waveguides to deliver the laser excitation light to the sample and collecting the resulting emission, simplifying the optical requirements associated with traditional SMD instruments by eliminating the need for optical alignment and simplification of the optical train. Additionally, the use of a vertical cavity surface emitting laser and a single photon avalanche diode serving as the excitation source and photon transducer, respectively, as well as a field programmable gate array (FPGA) integrated into the processing electronics assisted in reducing the instrument footprint. This small footprint SMD platform was tested using fluorescent microspheres and single AlexaFluor 660 molecules to determine the optimal operating parameters and system performance. As a demonstration of the utility of this instrument for biomolecular analyses, molecular beacons (MBs) were designed to probe bacterial cells for the gene encoding Gram-positive species. The ability to monitor biomarkers using this simple and portable instrument will have a number of important applications, such as strain-specific detection of pathogenic bacteria or the molecular diagnosis of diseases requiring rapid turn-around-times directly at the point-of-use.close5

Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection

BACKGROUND Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. METHODS We conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population. RESULTS In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo (MODIFY I: 17% [67 of 386] vs. 28% [109 of 395]; adjusted difference, −10.1 percentage points; 95% confidence interval [CI], −15.9 to −4.3; P<0.001; MODIFY II: 16% [62 of 395] vs. 26% [97 of 378]; adjusted difference, −9.9 percentage points; 95% CI, −15.5 to −4.3; P<0.001) and was significantly lower with actoxumab plus bezlotoxumab than with placebo (MODIFY I: 16% [61 of 383] vs. 28% [109 of 395]; adjusted difference, −11.6 percentage points; 95% CI, −17.4 to −5.9; P<0.001; MODIFY II: 15% [58 of 390] vs. 26% [97 of 378]; adjusted difference, −10.7 percentage points; 95% CI, −16.4 to −5.1; P<0.001). In prespecified subgroup analyses (combined data set), rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome. The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo; the rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea. CONCLUSIONS Among participants receiving antibiotic treatment for primary or recurrent C. difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo and had a safety profile similar to that of placebo. The addition of actoxumab did not improve efficacy. (Funded by Merck; MODIFY I and MODIFY II ClinicalTrials.gov numbers, NCT01241552 and NCT01513239.

Herbal remedy knowledge acquisition and transmission among the Yucatec Maya in Tabi, Mexico: a cross-sectional study

BACKGROUND: Ethnobotanical knowledge continues to be important for treating illness in many rural communities, despite access to health care clinics and pharmaceuticals. However, access to health care clinics and other modern services can have an impact on the distribution of medical ethnobotanical knowledge. Many factors have been shown to be associated with distributions in this type of knowledge. The goal of the sub-analyses reported in this paper was to better understand the relationship between herbal remedy knowledge, and two such factors, age and social network position, among the Yucatec Maya in Tabi, Yucatan. METHODS: The sample consisted of 116 Yucatec Maya adults. Cultural consensus analysis was used to measure variation in herbal remedy knowledge using competence scores, which is a measure of participant agreement within a domain. Social network analysis was used to measure individual position within a network using in-degree scores, based on the number of people who asked an individual about herbal remedies. Surveys were used to capture relevant personal attributes, including age. RESULTS: Analysis revealed a significant positive correlation between age and the herbal medicine competence score for individuals 45 and under, and no relationship for individuals over 45. There was an insignificant relationship between in-degree and competence scores for individuals 50 and under and a significant positive correlation for those over 50. CONCLUSIONS: There are two possible mechanisms that could account for the differences between cohorts: 1) knowledge accumulation over time; and/or 2) the stunting of knowledge acquisition through delayed acquisition, competing treatment options, and changes in values. Primary ethnographic evidence suggests that both mechanisms may be at play in Tabi. Future studies using longitudinal or cross-site comparisons are necessary to determine the whether and how the second mechanism is influencing the different cohorts.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Gobernabilidad y democracia en la universidad pública latinoamericana: Argentina y México en perspectiva comparada

Este es un breve ensayo sobre el poder, la gobernabilidad y la gobernanza institucional de las universidades públicas contemporáneas de Argentina y México. Desde una perspectiva comparada, se ofrece un análisis de las formas de gobierno y de las orientaciones del cambio institucional en la dimensión política observados en varios casos en los últimos años. El argumento central es que es posible identificar cuatro grandes orientaciones de cambio y una suerte de tensión esencial en la esfera política y de gobierno universitario. Las orientaciones se pueden ordenar en torno a dos grandes ejes analíticos: el de la concentración del poder, y en la del ejercicio del poder. La tensión puede formularse del siguiente modo: la persistencia histórica y práctica de la lógica de la gobernabilidad universitaria versus la emergencia de la lógica moderna de la gobernanza institucional. A partir del concepto de configuración institucional de los problemas del poder y el gobierno universitario, se exploran algunos de los hechos y de las implicaciones de los procesos de cambio en las relaciones entre la gobernabilidad y la democracia en las universidades públicas de América Latina